Transplant rejection occurs when the immune system of the recipient of a transplant attacks a transplanted organ or tissue. Thus, effective suppression of the immune response is known as a main factor determining the success of transplantation. In this regard, the development of immunosuppressive medications has brought about exceptional advances in the transplantation of organs and tissues and the treatment of autoimmune diseases and has made a great contribution to the study of the in vivo mechanism of immune responses to the transplanted organ or tissue.
As described, immunosuppressive drugs were developed to inhibit or attenuate transplant rejection. An example is cyclosporine A (U.S. Pat. No. 4,117,118) produced from Tolypocladium inflatum, a soil fungus. These immunosuppressive drugs not only help realize clinically successful organ transplantation, but also suggest the therapeutic use thereof in treating autoimmune diseases. Even though they are required to act selectively and specifically for T-cells only, conventional immunosuppressive drugs have an influence on a wide range of cellular functions, including general signal pathways, causing side effects on other organs, which are healthy (see. S.-H. Lee et al., Korean J. Immunology, 19:375˜389 (1997)). For instance, cyclosporine A is known to show side effects of chronic liver diseases and hypertension after heart transplantation (see: J. E. F. Reynolds, et al., Martindale The Extra Pharmacopoeia, 31st ed., pp. 557-562, Royal Pharmaceutical Society, London, 1996). Many attempts have been made to develop novel immunosuppressive drugs free of side effects. FK-506 has recently been discovered to be an immunosuppressant, and has been commercialized. However, side effects of this drug have also been found (Clin. Transplantation, 11: 237˜242 (1997)).
In China, vegetable worms, together with Korean ginseng, have long been used as precious materials in medicinal cuisine for special people in the aristocratic classes. Vegetable worms are a kind of medicinal fungus produced as a result of the parasitism of vegetable worms on insects. In high temperature and moisture conditions, the vegetable worms, which are actually fungus, infect living insects, proliferate therein to kill the host insects, and form fruiting bodies on the surface of the host insects. As used herein, the term “vegetable worm”, is intended to primarily refer to Cordyceps sinensis, a parasite on larvae of the Hepialidae family, but at present generally refers to all fungi attacking arthropods, such as spiders.
Cordyceps sinensis breaks down into 10.8% water, 8.4% lipids, 25˜32% crude proteins, 23.9% carbohydrates, and 18.5% crude fibers. In this vegetable worm are found 17 different amino acids, including 8 essential amino acids. Also, it contains a trace amount of cordycepin, 7.6% of D-mannitol and 11.2% of polysaccharides, all known as medicinally active materials. Cordycepin, a derivative of the nucleoside adenosine, is an isomer of quinic acid, known to show anti-cancer activity.
Various medicinally valuable activities of extracts from vegetable worms discovered thus far include antibacterial activity (Staphylococcus, Streptococcus, Bacterium mallei, Bacillus anthracis, Pasteurella suiseptica, Microsporum gypseum, and Microsporum lanosum), activity on the central nervous system (sedative, anticonvulsant activity), the respiratory system (bronchial asthma healing, expectorant activity) and the cardiovascular system (stabilization of heart beats, reduction of cholesterol level, anti-hypoxia activity), anticancer activity, immuno potentiation, anti-fatigue activity, and anti-aging activity.
However, nowhere has the use of vegetable worm extracts as an immunosuppressant been disclosed in the prior art.
Leading to the present invention, intensive and thorough research on an immunosuppressant entailing no side effects, conducted by the present inventors, resulted in the finding that an extract from vegetable worm mycelia significantly inhibits the immune response to transplanted organs or tissues.